4.7 Article

Regional subcortical shape analysis in premanifest Huntington's disease

期刊

HUMAN BRAIN MAPPING
卷 40, 期 5, 页码 1419-1433

出版社

WILEY
DOI: 10.1002/hbm.24456

关键词

circuit; premanifest Huntington's disease; shape; subcortical structures; subregion

资金

  1. National Institutes of Health [NIH R01 EB008171, NIH R01 EB000975, NIH P41 EB015909, NIH P50 NS091856, NIH R21 NS088302]
  2. CHDI Foundation [A3917]
  3. National Institute of Neurological Disorders and Stroke [NS40068]
  4. National Key R&D Program of China [2017YFC0112404]
  5. Shunde International Joint Research Institute Start-up Grant [20150306]
  6. National Natural Science Foundation of China [NSFC 81501546]

向作者/读者索取更多资源

Huntington's disease (HD) involves preferential and progressive degeneration of striatum and other subcortical regions as well as regional cortical atrophy. It is caused by a CAG repeat expansion in the Huntingtin gene, and the longer the expansion the earlier the age of onset. Atrophy begins prior to manifest clinical signs and symptoms, and brain atrophy in premanifest expansion carriers can be studied. We employed a diffeomorphometric pipeline to contrast subcortical structures' morphological properties in a control group with three disease groups representing different phases of premanifest HD (far, intermediate, and near to onset) as defined by the length of the CAG expansion and the participant's age (CAG-Age-Product). A total of 1,428 magnetic resonance image scans from 694 participants from the PREDICT-HD cohort were used. We found significant region-specific atrophies in all subcortical structures studied, with the estimated abnormality onset time varying from structure to structure. Heterogeneous shape abnormalities of caudate nuclei were present in premanifest HD participants estimated furthest from onset and putaminal shape abnormalities were present in participants intermediate to onset. Thalamic, hippocampal, and amygdalar shape abnormalities were present in participants nearest to onset. We assessed whether the estimated progression of subcortical pathology in premanifest HD tracked specific pathways. This is plausible for changes in basal ganglia circuits but probably not for changes in hippocampus and amygdala. The regional shape analyses conducted in this study provide useful insights into the effects of HD pathology in subcortical structures.

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